Yasuo Koike

Chubu University, Касугай, Aichi, Japan

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Publications (138)163.05 Total impact

  • Autonomic Neuroscience 12/2013; 179(s 1–2):175. · 1.85 Impact Factor
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    ABSTRACT: Background: Lifestyle modification is associated with a substantially decreased risk of cardiovascular events. However, the role of lifestyle intervention for secondary prevention in patients with noncardioembolic ischemic stroke is inadequately defined. We assessed the hypothesis that lifestyle intervention can reduce the onset of new vascular events in patients with noncardioembolic mild ischemic stroke. Methods: We conducted an observer-blind randomized controlled trial that enrolled 70 patients (48 men, mean age 63.5 years) with acute noncardioembolic mild ischemic stroke. The patients were allocated in equal numbers to a lifestyle intervention group or a control group. We performed lifestyle interventions, which comprised exercise training, salt restriction and nutrition advice for 24 weeks. Then all patients were prospectively followed up for occurrence of the primary endpoints, including hospitalization due to stroke recurrence and the onset of other vascular events. We also evaluated systolic blood pressure (SBP) at the clinic and at home, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hemoglobin A1c (HbA1c) and high-sensitivity C-reactive protein (hs-CRP) to compare the efficacy of the lifestyle interventions. Results: This trial was terminated earlier than expected because of the prespecified early stopping rule for efficacy. After the 24-week intervention period, the intervention group showed a significant increase in daily physical activity and a significant decrease in salt intake (physical activity, p = 0.012; salt intake, p < 0.001), with a significant difference between the randomized groups (physical activity, p < 0.001; salt intake, p = 0.018). Similarly, blood pressure was decreased and the HDL-C levels were increased in the intervention group (SBP, p < 0.001; HDL-C, p = 0.018), with significant differences between the randomized groups (SBP, p < 0.001; HDL-C, p = 0.022). In contrast, LDL-C, HbA1c and hs-CRP tended to decrease in the intervention group, but this decrease did not achieve significance. After a median follow-up period of 2.9 years, 12 patients allocated to the control group and 1 patient in the lifestyle intervention group experienced at least 1 vascular event. A sequential plans analysis indicated the superiority of the lifestyle intervention in interim analysis. Kaplan-Meier survival curves after the log-rank test showed a significant prognostic difference between the randomized groups (p = 0.005). Conclusions: Lifestyle intervention with appropriate medication is beneficial for reducing the incidence of new vascular events and improving vascular risk factors in patients with noncardioembolic mild ischemic stroke.
    Cerebrovascular Diseases 09/2013; 36(2):88-97. · 2.81 Impact Factor
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    ABSTRACT: PURPOSE: Although the number of apnea-hypopnea episodes per hour apnea-hypopnea index (AHI) is typically used to evaluate sleep-disordered breathing (SDB) in adults, it does not provide an accurate characterization of SDB in children. We investigated differences in SDB patterns in children and adults to evaluate SDB severity in children. MATERIALS AND METHODS: Fifteen adults (mean age, 45.3±8.4years) and 15 children (mean age, 6.7±3.9years) with adenotonsillar hypertrophy underwent standard polysomnography. The change of oxygen saturation (ΔSpO2) was defined as the difference between baseline SpO2 during stable nighttime breathing and the lowest SpO2 accompanied by an apnea-hypopnea event. The number of apnea-hypopnea episodes was determined using two different criteria to define an episode (criterion 1: cessation of airflow for at least 10s; criterion 2: cessation of airflow for at least two consecutive breaths). RESULTS: Mean ΔSpO2 accompanied by obstructive apneas lasting ≤10s was significantly greater in children than in adults, although there was no significant difference in the duration of apnea-hypopnea episodes. The slope of the regression line between ΔSpO2 and apnea-hypopnea duration in children was greater than in adults (P<0.005). AHI in children was higher when calculated using criterion 2 compared to criterion 1 (10.9±9.4 vs. 6.5±4.9/h, P=0.003). CONCLUSIONS: ΔSpO2 is a good indicator of SDB severity in children, and should therefore be considered in the diagnosis and treatment of pediatric SDB along with AHI.
    American journal of otolaryngology 02/2013; · 0.77 Impact Factor
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    ABSTRACT: Background Short sleep duration is associated with an increased risk of cardiovascular disease and all-cause mortality, although a relationship with atherosclerosis in the elderly remains unclear.Methods Eighty-six volunteers aged ≥65 years (mean, 73.6 ± 4.9 years) were evaluated for insomnia. Total sleep time (TST) and sleep efficiency were measured by actigraphy. Subjective symptoms were assessed with the Pittsburgh Sleep Quality Index (PSQI). Atherosclerosis was evaluated using ultrasonographic measurements of carotid intima-media thickness (IMT).ResultsIMT was significantly greater and sleep efficiency was significantly lower in subjects with TST ≤5 h than those with TST >7 h (1.3 ± 0.5 vs. 0.9 ± 0.3 mm; P = 0.009; 91.0 ± 6.0 vs. 81.6 ± 11.3%, P = 0.03, respectively). IMT was also significantly greater in the insomnia group than the noninsomnia group (1.3 ± 0.5 vs. 1.1 ± 0.4 mm; P = 0.03). IMT was significantly correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and TST (SBP: r = 0.49, P < 0.0001; DBP: r = 0.33, P = 0.0021; TST: r = -0.28, P = 0.010). Multiple regression analysis revealed that SBP, TST, and the PSQI were significant contributing factors for increased IMT (SBP: coefficient β = 0.56, P = 0.0001; TST: coefficient β = -0.32, P = 0.005; PSQI: coefficient β = 0.22, P = 0.05).Conclusions High blood pressure, short sleep duration (≤5 h), poor sleep, and insomnia were associated with atherosclerosis risk leading to cardiovascular disease in the elderly.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.107.
    American Journal of Hypertension 08/2012; 25(11):1149-55. · 3.67 Impact Factor
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    ABSTRACT: Complex sleep apnea syndrome (CompSAS) is diagnosed after an elimination of obstructive events with continuous positive airway pressure (CPAP), when a central apnea index ≥5/h or Cheyne-Stokes respiration pattern emerges in patients with obstructive sleep apnea syndrome (OSAS). However, the pathophysiology of CompSAS remains controversial. Of the 281 patients with suspected OSAS, all of whom underwent polysomnography conducted at Nagoya University Hospital, we enrolled 52 patients with apnea-hypopnea index ≥15/h (age 51.4 ± 13.3 years). The polysomnographic findings, left ventricular ejection fraction (LVEF), and nasal resistance were compared between the CompSAS patients and OSAS patients. Forty-three patients were diagnosed with OSAS and nine patients with central sleep apnea syndrome by natural sleep PSG. Furthermore, 43 OSAS patients were classified into the OSAS patients (OSAS group, n = 38) and the CompSAS patients (CompSAS group, n = 5) by the night on CPAP PSG. The nasal resistance was significantly higher in CompSAS group than in OSAS group (0.30 ± 0.10 vs. 0.19 ± 0.07 Pa/cm(3)/s, P = 0.004). The arousal index, percentage of stage 1 sleep, and oxygen desaturation index were significantly decreased, and the percentage of stage REM sleep was significantly increased in the OSAS group with the initial CPAP treatment, but not in the CompSAS group. In addition, the patients with CompSAS showed normal LVEF. CPAP intolerance secondary to an elevated nasal resistance might relate to frequent arousals, which could presumably contribute to an increase in central sleep apnea. Further evaluation in a large study is needed to clarify the mechanism of CompSAS.
    Sleep And Breathing 08/2011; 16(3):747-52. · 2.26 Impact Factor
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    ABSTRACT: This study aimed to identify the recurrence rate and risk factors or clinical variables predictive of vascular events after mild ischemic stroke (IS). From December 2006 to September 2007, patients with acute IS with a modified Rankin Scale of 0∼1 were consecutively enrolled in this study. Variables including sex, family history of vascular disease, age, height, weight, stroke subtype, blood pressure, lipid profile, fasting glucose, HbA1c, smoking, alcohol consumption, exercise habits, waist circumference, ankle-brachial pressure index, salt intake and physical activity were assessed. The primary outcome was stroke recurrence or other vascular events such as myocardial infarction, angina pectoris, and peripheral artery disease. Survival curves were calculated by Kaplan-Meier survival analysis, and hazard ratios for recurrence were determined by univariate and multivariate Cox proportional hazards regression models. A total of 102 mild IS patients (78 men and 24 women, mean age 64 years) were successfully followed for 3 years. Of those 102 patients, 25 (24.5%) had stroke recurrence, and 4 (3.9%) had a coronary event. Among the variables studied, abnormal ankle-brachial pressure index, metabolic syndrome, stroke subtypes, salt intake and poor lifestyle management were significant independent predictors of stroke recurrence or cardiovascular events. In mild IS patients within 3 years after onset, not only pathophysiological factors but also lifestyle factors can aid in the identification of patients at high risk for recurrence.
    Cerebrovascular Diseases 01/2011; 31(4):365-72. · 2.81 Impact Factor
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    ABSTRACT: Continuous positive airway pressure (CPAP) therapy has been shown to be effective in alleviating the underlying obstruction as well as reducing patients' excessive sleepiness and improving their functioning and health-related quality of life. However, residual excessive sleepiness is observed in some patients even though CPAP therapy eliminates sleep apnea and desaturation. The aim of this study was to determine the prognostic effect of actigraphic sleep-wake rhythm evaluation in the management of patients with obstructive sleep apnea syndrome (OSAS) treated with CPAP. Eighteen patients with OSAS diagnosed by standard polysomnography (PSG; 48.1 ± 12.5 years) were enrolled in this study. The sleep-wake parameters were determined by actigraphy before and after 1 month of CPAP treatment, and results were compared with PSG data. In addition, data obtained before CPAP were compared with those measured after 1 month of CPAP treatment. The total sleep time (TST) and sleep efficiency using PSG were significantly correlated with those using actigraphy. Bland-Altman plots of TST and sleep efficiency confirmed good agreement between PSG and actigraphy data. Sleep efficiency significantly improved following CPAP compared to baseline, and sleep fragmentation and sleep fragmentation >5 min determined by actigraphy were significantly lower during CPAP therapy than at baseline. Movement was significantly lower on CPAP therapy than at baseline. Actigraphy provides a valuable sleep-wake rhythm assessment in outpatients with OSAS where PSG is difficult to perform.
    Respiration 12/2010; 82(2):136-41. · 2.92 Impact Factor
  • Nosotchu 01/2010; 32(1):19-26.
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    ABSTRACT: Cumulative sleep deprivation may increase the risk of psychiatric disorders, other disorders, and accidents. We examined the effect of insufficient sleep on cognitive function, driving performance, and cerebral blood flow in 19 healthy adults (mean age 29.2 years). All participants were in bed for 8h (sufficient sleep), and for <4h (insufficient sleep). The oxyhaemoglobin (oxyHb) level by a word fluency task was measured with a near-infrared spectroscopy recorder on the morning following sufficient and insufficient sleep periods. Wisconsin card sorting test, continuous performance test, N-back test, and driving performance were evaluated on the same days. The peak oxyHb level was significantly lower, in the left and right frontal lobes after insufficient sleep than after sufficient sleep (left: 0.25+/-0.13 vs. 0.74+/-0.33 mmol, P<0.001; right: 0.25+/-0.09 vs. 0.69+/-0.44 mmol, P<0.01). The percentage of correct responses on CPT after insufficient sleep was significantly lower than that after sufficient sleep (96.1+/-4.5 vs. 86.6+/-9.8%, P<0.05). The brake reaction time in a harsh-braking test was significantly longer after insufficient sleep than after sufficient sleep (546.2+/-23.0 vs. 478.0+/-51.2 ms, P<0.05). Whereas there were no significant correlations between decrease in oxyHb and the changes of cognitive function or driving performance between insufficient sleep and sufficient sleep. One night of insufficient sleep affects daytime cognitive function and driving performance and this was accompanied by the changes of cortical oxygenation response.
    Neuroscience Letters 12/2009; 469(2):229-33. · 2.03 Impact Factor
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    ABSTRACT: Growth hormone-releasing peptide (GHRP) may act directly on the myocardium and improve left ventricular (LV) function, suggesting a potential new approach to the treatment of cardiomyopathic hearts. The present study tested the hypothesis that the beneficial cardiac effects of GHRP might include attenuation of myocardial oxidative stress. Dilated cardiomyopathic TO-2 hamsters were injected with GHRP-2 (1 mg/kg) or saline from 6 to 12 weeks of age. F1B hamsters served as controls. Untreated TO-2 hamsters progressively developed LV dilation, wall thinning, and systolic dysfunction between 6 and 12 weeks of age. Marked myocardial fibrosis was apparent in untreated hamsters at 12 weeks of age in comparison with F1B controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and the concentration of 4-hydroxynonenal (4-HNE) was increased in the hearts of untreated TO-2 hamsters. Treatment with GHRP-2 attenuated the progression of LV remodeling and dysfunction, as well as myocardial fibrosis, in TO-2 hamsters. GHRP-2 also inhibited both the decrease in the GSH/GSSG ratio and the increase in the concentration of 4-HNE in the hearts of TO-2 hamsters. GHRP-2 can suppress the increase in the level of myocardial oxidative stress, leading to attenuation of progressive LV remodeling and dysfunction in dilated cardiomyopathic hamsters. (Circ J 2010; 74: 163 - 170).
    Circulation Journal 11/2009; 74(1):163-70. · 3.58 Impact Factor
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    ABSTRACT: Asymmetrical septal hypertrophy and impaired left ventricular (LV) diastolic function are common echocardiographic features of hypertrophic cardiomyopathy (HCM). However, it is difficult to differentiate nonobstructive HCM from hypertensive LV hypertrophy (H-LVH). Standard echocardiography and tissue Doppler imaging were performed in 14 patients with HCM, 16 patients with H-LVH, and 21 control subjects. Endomyocardial radial strain, systolic strain rate (SR), and the early diastolic SR at the posterior and septal segments of the LV short axis were calculated. Endomyocardial peak strain (epsilon) and the absolute value of peak early diastolic SR at the posterior segment were significantly smaller in patients with HCM than in those with H-LVH, whereas the thickness of the LV posterior wall did not differ between these 2 groups. Multivariate analysis of discrimination, including the ratio of interventricular septal thickness and posterior wall thickness (IVST/PWT), epsilon, and SR parameters, between HCM and H-LVH patients revealed that epsilon at the LV posterior segment was the highest discriminant parameter (discriminant coefficient: -14.6, P=0.012). The epsilon at the posterior segment significantly correlated with early diastolic mitral annular velocity. Endomyocardial radial strain imaging may prove informative for discriminating between HCM and H-LVH.
    Circulation Journal 10/2009; 73(12):2294-9. · 3.58 Impact Factor
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    ABSTRACT: "Microarousals" during sleep have not been analyzed systematically. We investigated the importance of "microarousals" (lasting 1.5-3 s). Standard polysomnography including esophageal pressure (Pes) assessment was performed on ten patients (aged 54.0 +/- 5.0 years) with respiratory effort-related arousal > or =5/h. We measured the number of arousals per hour (American Sleep Disorders Association (ASDA) arousal index) and the number of microarousals lasting 1.5-3 s per hour (mASDA arousal index). On the night after the baseline sleep study, we performed overnight continuous positive airway pressure (CPAP) titration. mASDA arousals, characterized by lower Pes values, were observed more frequently in patients with sleep-disordered breathing. The Pes results did not differ significantly between ASDA and mASDA arousals (-15.6 +/- -5.0 vs -15.0 +/- -4.4 cmH(2)O). mASDA arousals were significantly improved by CPAP treatment (mASDA arousals, 82.6 +/- 60.1 vs 6.0 +/- 1.4/h). mASDA arousals were characterized by an increase in Pes. mASDA arousals are thus key to our understanding of clinical manifestations in patients with sleep-disordered breathing.
    Sleep And Breathing 06/2009; 13(4):369-73. · 2.26 Impact Factor
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    ABSTRACT: The clinical efficacy of exercise training in individuals with heart failure is well established, but the mechanism underlying such efficacy has remained unclear. An imbalance between cardiac hypertrophy and angiogenesis is implicated in the transition to heart failure. We investigated the effects of exercise training on cardiac pathophysiology in hypertensive rats. Dahl salt-sensitive rats fed a high-salt diet from 6 weeks of age were assigned to sedentary or exercise (swimming)-trained groups at 9 weeks. Exercise training attenuated the development of heart failure and increased survival, without affecting blood pressure, at 18 weeks. It also attenuated left ventricular concentricity without a reduction in left ventricular mass or impairment of cardiac function. Interstitial fibrosis was increased and myocardial capillary density was decreased in the heart of sedentary rats, and these effects were attenuated by exercise. Exercise potentiated increases in the phosphorylation of Akt and mammalian target of rapamycin observed in the heart of sedentary rats, whereas it inhibited the downregulation of proangiogenic gene expression apparent in these animals. The abundance of the p110alpha isoform of phosphatidylinositol 3-kinase was decreased, whereas those of the p110gamma isoform of phosphatidylinositol 3-kinase and the phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase were increased, in the heart of sedentary rats, and all of these effects were prevented by exercise. Thus, exercise training had a beneficial effect on cardiac remodeling and attenuated heart failure in hypertensive rats, with these effects likely being attributable to the attenuation of left ventricular concentricity and restoration of coronary angiogenesis through activation of phosphatidylinositol 3-kinase(p110alpha)-Akt-mammalian target of rapamycin signaling.
    Hypertension 05/2009; 53(4):701-7. · 6.87 Impact Factor
  • Journal of Cardiac Failure - J CARD FAIL. 01/2009; 15(7).
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    ABSTRACT: Current lifestyles often involve activities during the day and at night, and disruption of habits and sleep–wake rhythms may result in circadian rhythm disorders. We assessed the sleep habits and lifestyle habits in 52 subjects using the Japanese-language version of Horne and Ostberg's Morningness-Eveningness Questionnaire and the Tokyo Neurosciences General Laboratory Formula Examination of Life Habits. Of the 52 subjects, 9.6% were morning-types, 71.2% were intermediate-types, and 19.2% were evening-types. Of the evening-types, 40% had a variation in sleep time of more than two hours, and 20% had a variation in awakening time of more than two hours. Approximately 80% of the morning-types and 20% of the evening-types reported pleasant awakening experiences. Assessment of actual conditions of sleep and lifestyle habits using simple and highly reliable questionnaires may be useful in the prevention of sleep disorders and in the improvement of sleep and lifestyle habits.
    Biological Rhythm Research 01/2009; 40(2):121-127. · 1.22 Impact Factor
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    ABSTRACT: Sleep disturbances manifesting as insomnia, daytime sleepiness, fatigue, and other symptoms are frequently found in patients with end-stage renal disease that is being treated with dialysis. Many factors, including neurosis, uremic symptoms, dialysis drugs, and sleep-wake rhythms have been suggested as potential causes for these sleep disturbances. We examined sleep apnea/hypopnea and heart rate variability (HRV) reflecting autonomic activity in hemodialysis patients on their hemodialysis and non-hemodialysis days using a home medical care device (Morpheus C, TEIJIN). Eleven hemodialysis patients and 14 healthy adults were enrolled in this study. We calculated the number of apnea/hypopnea episodes per hour (apnea/hypopnea index: AHI) and HRV (percentage of R-R intervals that differ by at least 50 ms from the previous interval: pNN50, very low frequency: VLF, low frequency: LF, high frequency: HF and LF/ HF). There was no significant difference in the AHI between hemodialysis and non-hemodialysis days. The heart rate in hemodialysis patients on non-hemodialysis days was significantly higher than in the controls, whereas the pNN50 was significantly lower in hemodialysis patients on non-hemodialysis days than in the controls. Although VLF was significantly lower in hemodialysis patients on non-hemodialysis days compared to the controls, there were no significant differences in LF, HF or LF/HF between the two groups. Hemodialysis itself might not be an important contributing factor in sleep-related breathing disturbances. The simultaneous analysis of HRV reflecting autonomic activity and sleep-disordered breathing on both hemodialysis and non-hemodialysis days provides important information.
    Nagoya journal of medical science 09/2008; 70(3-4):83-8.
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    ABSTRACT: The aim of this study was to clarify the interaction of lateral and supine sleeping positions with upper airway morphology in patients with obstructive sleep apnea syndrome (OSAS). Thirty-one patients with OSAS, whose apnea/hypopnea index (AHI: number of episodes of apnea or hypopnea per hour) was over 15, were enrolled in this study. Subjects were divided in two groups according to positional effects on their AHI. In six patients, a lateral posture decreased the AHI by 50% and more (responders); in the remaining 25, lateral positioning decreased the AHI by less than 50% or even increased the AHI (nonresponders). AHI and body mass index (BMI) of the responders tended to be lower and their mean age was younger than those of nonresponders, but these differences were not statistically significant. We compared the upper airway morphology between the responders and the nonresponders regarding the tonsil size, tongue position (modified Mallanpati grade, reflecting the space between the tongue and soft palate) and the width of the fauces and retroglossal space. In addition, we compared nasal resistance between the groups using active rhinomanometry. The width of the fauces was significantly greater (P=0.041) among the responders than among the nonresponders. However, the other parameters were not consistently different between the two, and these differences were not statistically significant either. The distance between the fauces was the sole morphological feature to distinguish the responders and the nonresponders to the positional therapy in patients with OSAS. Lateral positioning during sleep might be a recommended sleep hygiene for OSAS patients with wide fauces.
    Auris, nasus, larynx 08/2008; 36(3):305-9. · 0.58 Impact Factor
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    ABSTRACT: Objective: Cardiac hypertrophy is common in diabetes and an independent risk factor for cardiac morbidity and mortality. We investigated the effects of pioglitazone on cardiac hypertrophy and hypertrophic signaling in Dahl salt-sensitive hypertensive rats. Methods: Dahl salt-sensitive rats were fed a high-salt diet from 7 weeks of age and treated with pioglitazone (2.5 mg/kg per day) or vehicle from 7 to 11 weeks. Results: The vehicle-treated rats developed left ventricular hypertrophy and fibrosis as well as left ventricular diastolic dysfunction. The serum level of adiponectin and the phosphorylation of AMP-activated protein kinase in the myocardium did not differ between the vehicle-treated rats and control rats maintained on a normal diet. The phosphorylation of Akt, mammalian target of rapamycin, and p70S6 kinase as well as the total protein content were increased in the heart of vehicle-treated rats compared with control rats, and these changes were blocked by treatment with pioglitazone. Pioglitazone treatment also ameliorated left ventricular hypertrophy and fibrosis, improved diastolic function, and increased both the serum adiponectin concentration and the level of AMP-activated protein kinase phosphorylation in the heart. Conclusions: Long-term administration of pioglitazone attenuated left ventricular hypertrophy and fibrosis as well as inhibited phosphorylation of mammalian target of rapamycin and p70S6 kinase in the heart of hypertensive rats. The beneficial cardiac effects of pioglitazone are likely attributable, at least partly, both to the activation of AMP-activated protein kinase signaling through stimulation of adiponectin secretion and to the inhibition of Akt signaling.
    Journal of Hypertension 07/2008; 26(8):1669-1676. · 4.22 Impact Factor
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    ABSTRACT: Obstructive sleep apnea syndrome (OSAS) is associated with increases in cardiovascular morbidity and mortality. Vascular changes in individuals with OSAS have not been fully elucidated, however. The possible impact of OSAS on the extent of aortic pressure augmentation (AG), an indicator of cardiovascular risk, was investigated. Forty-five consecutive male patients aged 35 to 78 years (56.0+/-9.6 years) who were referred to the sleep clinic of Nagoya University Hospital for screening and treatment of OSAS and 71 age-matched healthy men were enrolled in the study. AG was derived from the pressure waveform measured at the radial artery by applanation tonometry. The number of apnea and hypopnea episodes per hour (apnea-hypopnea index [AHI]) was determined by standard polysomnography. AG was significantly greater in OSAS patients than in controls (9.0+/-4.1 vs. 6.4+/-3.4 mmHg, p<0.001), and it was significantly reduced in 19 OSAS patients treated with continuous positive airway pressure. AG was also significantly correlated with the AHI (r=0.562, p<0.001) and age (r=0.356, p=0.016) but not with the serum concentrations of low and high density lipoprotein-cholesterol, triglyceride, or glycosylated hemoglobin. Stepwise multiple regression analysis revealed that the AHI was the most significant contributing factor to the increased AG in OSAS patients (beta=0.109, r=0.530, p<0.001). OSAS may thus have an adverse effect on vascular function that can be ameliorated by appropriate treatment.
    Hypertension Research 07/2008; 31(6):1109-14. · 2.79 Impact Factor
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    ABSTRACT: Oxidative stress is implicated in cardiac remodeling and failure. We tested whether xanthine oxidase (XO) inhibition could decrease myocardial oxidative stress and attenuate left ventricular (LV) remodeling and dysfunction in the TO-2 hamster model of dilated cardiomyopathy. TO-2 hamsters were randomized to treatment with the XO inhibitor, allopurinol, or vehicle from 6 to 12 weeks of age. F1B hamsters served as controls. TO-2 hamsters treated with vehicle progressively developed severe LV systolic dysfunction and dilation between 6 and 12 weeks. Marked cardiac fibrosis was apparent in these hamsters at 12 weeks in comparison with F1B controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and malondialdehyde levels were increased in the hearts of vehicle-treated TO-2 hamsters. Treatment with allopurinol from 6 to 12 weeks attenuated LV dysfunction and dilation as well as myocardial fibrosis and the upregulation of a fetal-type cardiac gene. Allopurinol also inhibited both the decrease in GSH/GSSG ratio and the increase in malondialdehyde levels in the heart. These results indicate that chronic XO inhibition with allopurinol attenuates LV remodeling and dysfunction as well as myocardial oxidative stress in this model of heart failure. Allopurinol may prove beneficial for the treatment of heart failure.
    Journal of cardiac failure 05/2008; 14(3):238-44. · 3.25 Impact Factor

Publication Stats

701 Citations
163.05 Total Impact Points

Institutions

  • 2011–2013
    • Chubu University
      • College of Life and Health Sciences
      Касугай, Aichi, Japan
  • 1993–2009
    • Nagoya University
      • • Graduate School of Medicine
      • • Division of Neurology
      • • School of Health Sciences
      Nagoya-shi, Aichi-ken, Japan
  • 2007
    • Kokura Memorial Hospital
      Kitakyūshū, Fukuoka, Japan
  • 1999
    • Nagoya Second Red Cross Hospital
      Nagoya, Aichi, Japan
  • 1995
    • Emory University
      • Department of Neurology
      Atlanta, GA, United States
  • 1994
    • Kyoto Daini Red Cross Hospital
      Kioto, Kyōto, Japan